Among women worldwide breast cancer is the most common cancer and the most common cause of death by cancer. Breast cancer is believed to be caused by a variety of factors, one of these factors being increased blood levels of estrogen. Much research has taken place in the field of estrogen receptor families and the differences between estrogen receptor cancer cells and normal estrogen receptor cells. The aim of such research has been to discover drugs which can treat breast cancer by suppressing production of estrogen in the body.
One such type of cancer comprises cells bearing estrogen receptor (ER+ cells). These are cells with a large number of estrogen receptors, typically around 200000 to 5 million. A normal non-cancerous estrogen receptor cell will have typically around 20000 to 80000 estrogen receptors. Cancer cells have an increased rate of division in the presence of estrogen, responding to even small quantities of the hormone, due to the large number of estrogen receptors.
Novel systemic therapies for breast cancer are discussed in Surgical Oncology 12 (2003) 277-287 (Soo Lo, Stephen R. D. Johnston). These include endocrine therapies such as pure anti-estrogens and selective estrogen receptor modulators (SERMs), monoclonal antibodies targeted against growth factor receptors, small molecule signal transduction inhibitors, vaccines and immunotherapy strategies, and anti-angiogenesis therapies.
One drug that has been shown to be effective in treatment of estrogen receptor positive cancer is tamoxifen. Tamoxifen is an example of a selective estrogen receptor modulator (SERM) acting as an antagonist to estrogen receptor positive cancerous cells by binding to the estrogen receptors on the cell surface and preventing binding of estrogen to the cells and thus inhibiting cell division. Even though it is an antagonist in breast tissue it acts as partial agonist on the endometrium and has been linked to endometrial cancer in some women. Therefore, endometrial changes, including cancer, are among tamoxifen's side effects.
It has also been suggested that a conjugate of tamoxifen and a porphyrin might be effective in the photodynamic treatment of cancer cells, whereby the porphyrin displays phototoxic activity on exposure to red light and has a stronger cell killing in MCF-7 breast cancer cells compared with an unconjugated porphyrin. Estradiol-porphyrin conjugates which selectively localise into estrogen receptor positive breast cancer cells for photodynamic therapy of breast cancer are also described in Bioinorganic & medicinal Chemistry 10 (2002) 3237-3243 (Swamy, James, Mohr, Hanson and Ray).
Other conjugates that have been researched for their effectiveness in treating cancer include antibody toxin conjugates. British Journal of Haemotology 2000, 110, 351-361 (Bolognesi, Polito et al.) discloses linking of ribosome inactivating proteins such as saporin to monoclonal antibodies for the treatment of Hodgkin's lymphoma. However, to date there has been no such product that has succeeded through the human trials into a licensed product.
Whilst the current drugs and therapies for treatment of cancer and in particular breast cancer on the market do slow down the division of these cancer cells, after a few years the cells mutate such that they are no longer effected by the drug and the drug becomes useless, with patients not responding to the treatment.
It is an aim therefore of the present invention to provide a new treatment for ER+ cancers, including in particular such breast cancers, which solves the above mentioned problems by destroying ER+ cancer cells rather than just reducing the rate of cell division of these cancer cells like the other SERM's and treatments do.
The above mentioned problems have been solved by the aspects and embodiments of the present invention outlined below.